Association of childhood traumatization and neuropsychiatric outcomes with altered plasma micro RNA-levels

Sandra Van der Auwera, Sabine Ameling, Katharina Wittfeld, Enrique d’Harcourt Rowold, Matthias Nauck, Henry Völzke, Karsten Suhre, Hani Najafi-Shoushtari, Jaicy Methew, Vimal Ramachandran, Robin Bülow, Uwe Völker, Hans J. Grabe

Research output: Contribution to journalArticle

Abstract

Childhood traumatization (CT) is associated with the development of several neuropsychiatric disorders in later life. Experimental data in animals and observational data in humans revealed evidence for biological alterations in response to CT that may contribute to its long-term consequences. This includes epigenetic changes in miRNA levels that contribute to complex alterations of gene expression. We investigated the association between CT and 121 miRNAs in a target sample of N = 150 subjects from the general population and patients from the Department of Psychiatry. We hypothesized that CT exhibits a long-term effect on miRNA plasma levels. We supported our findings using bioinformatics tools and databases. Among the 121 miRNAs 22 were nominally significantly associated with CT and four of them (let-7g-5p, miR-103a-3p, miR-107, and miR-142-3p) also after correction for multiple testing; most of them were previously associated with Alzheimer’s disease (AD) or depression. Pathway analyses of target genes identified significant pathways involved in neurodevelopment, inflammation and intracellular transduction signaling. In an independent general population sample (N = 587) three of the four miRNAs were replicated. Extended analyses in the general population sample only (N = 687) showed associations of the four miRNAs with gender, memory, and brain volumes. We gained increasing evidence for a link between CT, depression and AD through miRNA alterations. We hypothesize that depression and AD not only share environmental factors like CT but also biological factors like altered miRNA levels. This miRNA pattern could serve as mediating factor on the biological path from CT to adult neuropsychiatric disorders.

Original languageEnglish
JournalNeuropsychopharmacology
DOIs
Publication statusPublished - 1 Jan 2019

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MicroRNAs
Alzheimer Disease
Biological Factors
Depression
Population
Computational Biology
Epigenomics
Psychiatry
Databases
Inflammation
Gene Expression
Brain
Genes

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Van der Auwera, S., Ameling, S., Wittfeld, K., d’Harcourt Rowold, E., Nauck, M., Völzke, H., ... Grabe, H. J. (2019). Association of childhood traumatization and neuropsychiatric outcomes with altered plasma micro RNA-levels. Neuropsychopharmacology. https://doi.org/10.1038/s41386-019-0460-2

Association of childhood traumatization and neuropsychiatric outcomes with altered plasma micro RNA-levels. / Van der Auwera, Sandra; Ameling, Sabine; Wittfeld, Katharina; d’Harcourt Rowold, Enrique; Nauck, Matthias; Völzke, Henry; Suhre, Karsten; Najafi-Shoushtari, Hani; Methew, Jaicy; Ramachandran, Vimal; Bülow, Robin; Völker, Uwe; Grabe, Hans J.

In: Neuropsychopharmacology, 01.01.2019.

Research output: Contribution to journalArticle

Van der Auwera, S, Ameling, S, Wittfeld, K, d’Harcourt Rowold, E, Nauck, M, Völzke, H, Suhre, K, Najafi-Shoushtari, H, Methew, J, Ramachandran, V, Bülow, R, Völker, U & Grabe, HJ 2019, 'Association of childhood traumatization and neuropsychiatric outcomes with altered plasma micro RNA-levels', Neuropsychopharmacology. https://doi.org/10.1038/s41386-019-0460-2
Van der Auwera, Sandra ; Ameling, Sabine ; Wittfeld, Katharina ; d’Harcourt Rowold, Enrique ; Nauck, Matthias ; Völzke, Henry ; Suhre, Karsten ; Najafi-Shoushtari, Hani ; Methew, Jaicy ; Ramachandran, Vimal ; Bülow, Robin ; Völker, Uwe ; Grabe, Hans J. / Association of childhood traumatization and neuropsychiatric outcomes with altered plasma micro RNA-levels. In: Neuropsychopharmacology. 2019.
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